Diagnostic accuracy of postmortem imaging vs autopsy-A systematic review.

Background Postmortem imaging has been used for more than a century as a complement to medico-legal autopsies. The technique has also emerged as a possible alternative to compensate for the continuous decline in the number of clinical autopsies. To evaluate the diagnostic accuracy of postmortem imaging for various types of findings, we performed this systematic literature review. Data sources The literature search was performed in the databases PubMed, Embase and Cochrane Library through January 7, 2015. Relevant publications were assessed for risk of bias using the QUADAS tool and were classified as low, moderate or high risk of bias according to pre-defined criteria. Autopsy and/or histopathology were used as reference standard. Findings The search generated 2600 abstracts, of which 340 were assessed as possibly relevant and read in full-text. After further evaluation 71 studies were finally included, of which 49 were assessed as having high risk of bias and 22 as moderate risk of bias. Due to considerable heterogeneity - in populations, techniques, analyses and reporting - of included studies it was impossible to combine data to get a summary estimate of the diagnostic accuracy of the various findings. Individual studies indicate, however, that imaging techniques might be useful for determining organ weights, and that the techniques seem superior to autopsy for detecting gas Conclusions and Implications In general, based on the current scientific literature, it was not possible to determine the diagnostic accuracy of postmortem imaging and its usefulness in conjunction with, or as an alternative to autopsy. To correctly determine the usefulness of postmortem imaging, future studies need improved planning, improved methodological quality and larger materials, preferentially obtained from multi-center studies.

Diagnostic accuracy of different caries risk assessment methods. A systematic review.

OBJECTIVES: To evaluate the accuracy of different methods used to identify individuals with increased risk of developing dental coronal caries. DATA: Studies on following methods were included: previous caries experience, tests using microbiota, buffering capacity, salivary flow rate, oral hygiene, dietary habits and sociodemographic variables. QUADAS-2 was used to assess risk of bias. Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated. Quality of evidence based on ≥3 studies of a method was rated according to GRADE. SOURCES: PubMed, Cochrane Library, Web of Science and reference lists of included publications were searched up to January 2015. STUDY SELECTION: From 5776 identified articles, 18 were included. Assessment of study quality identified methodological limitations concerning study design, test technology and reporting. No study presented low risk of bias in all domains. Three or more studies were found only for previous caries experience and salivary mutans streptococci and quality of evidence for these methods was low. Evidence regarding other methods was lacking. For previous caries experience, sensitivity ranged between 0.21 and 0.94 and specificity between 0.20 and 1. Tests using salivary mutans streptococci resulted in low sensitivity and high specificity. For children with primary teeth at baseline, pooled LR for a positive test was 3 for previous caries experience and 4 for salivary mutans streptococci, given a threshold ≥10(5) CFU/ml. CONCLUSIONS: Evidence on the validity of analysed methods used for caries risk assessment is limited. As methodological quality was low, there is a need to improve study design. CLINICAL SIGNIFICANCE: Low validity for the analysed methods may lead to patients with increased risk not being identified, whereas some are falsely identified as being at risk. As caries risk assessment guides individualized decisions on interventions and intervals for patient recall, improved performance based on best evidence is greatly needed.

A systematic map of systematic reviews in pediatric dentistry--what do we really know?

OBJECTIVES: To identify, appraise and summarize existing knowledge and knowledge gaps in practice-relevant questions in pediatric dentistry. METHODS: A systematic mapping of systematic reviews was undertaken for domains considered important in daily clinical practice. The literature search covered questions in the following domains: behavior management problems/dental anxiety; caries risk assessment and caries detection including radiographic technologies; prevention and non-operative treatment of caries in primary and young permanent teeth; operative treatment of caries in primary and young permanent teeth; prevention and treatment of periodontal disease; management of tooth developmental and mineralization disturbances; prevention and treatment of oral conditions in children with chronic diseases/developmental disturbances/obesity; diagnosis, prevention and treatment of dental erosion and tooth wear; treatment of traumatic injuries in primary and young permanent teeth and cost-effectiveness of these interventions. Abstracts and full text reviews were assessed independently by two reviewers and any differences were solved by consensus. AMSTAR was used to assess the risk of bias of each included systematic review. Reviews judged as having a low or moderate risk of bias were used to formulate existing knowledge and knowledge gaps. RESULTS: Out of 81 systematic reviews meeting the inclusion criteria, 38 were judged to have a low or moderate risk of bias. Half of them concerned caries prevention. The quality of evidence was high for a caries-preventive effect of daily use of fluoride toothpaste and moderate for fissure sealing with resin-based materials. For the rest the quality of evidence for the effects of interventions was low or very low. CONCLUSION: There is an urgent need for primary clinical research of good quality in most clinically-relevant domains in pediatric dentistry.

Measuring GFR: a systematic review.

BACKGROUND: No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. STUDY DESIGN: Systematic review with meta-analysis of cross-sectional diagnostic studies. SETTING & POPULATION: Published original studies and systematic reviews in any population. SELECTION CRITERIA FOR STUDIES: Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. INDEX TESTS: Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. REFERENCE TEST: Renal inulin clearance measured under continuous inulin infusion and urine collection. RESULTS: Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%. LIMITATIONS: The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. CONCLUSIONS: At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

Pulp exposures in adults--choice of treatment among Swedish dentists.

This study comprises a survey of Swedish dentists'treatment preferences in cases of carious exposure of the dental pulp in adults.The survey was conducted as part of a comprehensive report on methods of diagnosis and treatment in endodontics, published in 2010 by the Swedish Council on Health Technology Assessment. A questionnaire was mailed to a random subsample of 2012 dental offices where one dentist at each office was requested to answer all questions. Each questionnaire contained one of three sets of questions about endodontic practice routines.Thus around one-third of the subsample received case-specific questions about treating carious exposure. Only general practitioners aged below 70 years were included.The final study sample comprised 412 participants.The dentists were presented with two case scenarios. In Case 1 a 22-year old patient had a deep carious lesion in tooth 36 and in Case 2 a 50-year old patient had a deep carious lesion in tooth 14.The participants were asked to nominate their treatment of choice: pulp capping, partial pulpotomy or pulpectomy. For Case 1, 17 per cent of the respondents selected pulpectomy; the corresponding rate for Case 2 was 47 per cent. Female gender and age group 25-49 years were predictive of selection of less invasive treatment options. However, according to recent guidelines (2011) from the National Board of Health and Wellfare, Swedish dentists are recommended to elect pulpectomy prior to pulp capping/partial pulpotomy when confronted with a tooth having a cariously exposed pulp in adults.

Treatment of pulps in teeth affected by deep caries - A systematic review of the literature.

BACKGROUND: This systematic review assesses the effect of methods commonly used to manage the pulp in cases of deep caries lesions, and the extent the pulp chamber remains uninfected and does not cause pulpal or periapical inflammatory lesions and associated tooth-ache over time. STUDY DESIGN: An electronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to March 2013. In addition, hand searches were carried out. Two reviewers independently evaluated abstracts and full-text articles. An article was read in full if at least one of the two reviewers considered the abstract potentially relevant. Altogether, 161 articles were read in full text. Of these, 24 studies fulfilled established inclusion criteria. Based on studies of at least moderate quality, the quality of evidence of each procedure was rated in four levels according to GRADE. RESULTS: No study reached the high quality level. Twelve were of moderate quality. The overall evidence was insufficient to assess which of indirect pulp capping, stepwise excavation, direct excavation and pulp capping/partial pulpotomy, pulpotomy or pulpectomy is the most effective treatment approach for teeth with deep caries. CONCLUSIONS: Because of the lack of good studies it is not possible to determine whether an injured pulp by deep caries can be maintained or whether it should be removed and replaced with a root canal filling. Both randomized studies and prospective observational studies are needed to investigate whether a pulp exposed to deep caries is best treated by measures intended to preserve it or by pulpectomy and root filling.

Adjunct methods for caries detection: a systematic review of literature.

OBJECTIVE: To assess the diagnostic accuracy of adjunct methods used to detect and quantify dental caries. STUDY DESIGN: A systematic literature search for relevant papers was conducted with pre-determined inclusion and exclusion criteria. Abstracts and full text articles were assessed independently by two reviewers. The study characteristics were compiled in tables and quality graded according to the QUADAS tool. The level of evidence for each diagnostic technology (fiber-optic methods, fluorescence methods, electrical methods) was based on studies of high or moderate quality according to the GRADE approach. RESULTS: Twenty-five reports fulfilled the inclusion criteria. One study was of high quality, 10 were graded as moderate, while the remaining 14 reports were of low quality. Electrical methods (ECM) and laser fluorescence (DIAGNOdent) displayed sensitivities and specificities around 70-80% regarding occlusal dentin lesions with a mean Youden's index of 0.52-0.54. The mean accuracy of laser fluorescence for detecting enamel and dentin lesions was 0.68 and 0.91, respectively. The heterogeneity of the published reports hampered the analysis. CONCLUSIONS: There was insufficient scientific evidence for diagnostic accuracy regarding fiber-optic methods and quantitative light-induced fluorescence (+OOO). The electrical methods and laser fluorescence could be useful adjuncts to visual-tactile and radiographic examinations, especially on occlusal surfaces in permanent and primary molars, but evidence was graded as limited (++OO). No conclusions could be drawn regarding the cost-effectiveness of the methods. There is an obvious need to standardize study designs for in vitro and in vivo validation of the different methods.

Is single reading with computer-aided detection (CAD) as good as double reading in mammography screening? A systematic review.

BACKGROUND: In accordance with European guidelines, mammography screening comprises independent readings by two breast radiologists (double reading). CAD (computer-aided detection) has been suggested to complement or replace one of the two readers (single reading + CAD).The aim of this systematic review is to address the following question: Is the reading of mammographic x-ray images by a single breast radiologist together with CAD at least as accurate as double reading? METHODS: The electronic literature search included the databases Pub Med, EMBASE and The Cochrane Library. Two independent reviewers assessed abstracts and full-text articles. RESULTS: 1049 abstracts were identified, of which 996 were excluded with reference to inclusion and exclusion criteria; 53 full-text articles were assessed for eligibility. Finally, four articles were included in the qualitative analysis, and one in a GRADE synthesis. CONCLUSIONS: The scientific evidence is insufficient to determine whether the accuracy of single reading + CAD is at least equivalent to that obtained in standard practice, i.e. double reading where two breast radiologists independently read the mammographic images.

Indications for fissure sealants and their role in children and adolescents.

The aim of this article is to summarize and interpret present knowledge and evidence on the effect of fissure sealing permanent first and second molars in children and adolescents with two commonly used materials: resin sealants and glass ionomer sealants. Also, to identify important gaps in our knowledge. The results show that the conclusions from systematic reviews differ in several aspects, and that important knowledge gaps still exist, such as the costs and benefits of sealing low- versus high-risk populations. The effect of sealing noncavitated caries lesions is uncertain and possible differences in effect between resin sealants and the high viscosity glass ionomers need to be investigated.

Economic aspects of the detection of occlusal dentine caries.

OBJECTIVE: To evaluate the cost of true-positive occlusal dentine caries detection in permanent molars assessed by: (I) visual-tactile examination, (II) visual-tactile examination combined with bitewing radiographs, and (III) selective radiographic examination of patients with lesions detected clinically. A second aim was to analyse the different strategies when the costs of the subsequent restorative care are considered. METHODS: A model analysis was applied owing to the lack of original articles. Sensitivity and specificity were calculated from a systematic review and included in vitro and in vivo studies of medium and high quality. The direct costs for examinations and restorative care were extracted from the costs of the Public Dental Service in Sweden (2006). RESULTS: The diagnostic costs per true-positive finding were dependent on the occurrence of occlusal caries and increased with decreasing prevalence. The strategy by which radiographs were exposed selectively on the basis of findings from visual-tactile examination resulted in higher initial costs compared with the first and second strategies. When the costs of the subsequent restorative care were added, the selective strategy was most beneficial by up to 26% savings per true-positive diagnosis. However, with this selective strategy, more cases of true-positive dentine caries were assumed would remain undetected as compared with the combined strategy with visual-tactile examination and radiographs for all. CONCLUSIONS: The cost for a true-positive caries diagnosis was inversely related to caries occurrence, and different diagnostic strategies may display contrasting outcomes when subsequent restorative care is taken into account.

Background factors associated with endodontic treatment due to caries in young permanent teeth.

OBJECTIVE: The aim of this retrospective cohort study was to assess the association between background factors and future endodontic treatment due to caries in young permanent teeth. MATERIAL AND METHODS: The material comprised all 19-year-olds born in 1979 in a city in Sweden who had experienced endodontic treatment due to caries in permanent teeth (n=105) and a control group with no endodontic treatment. From dental records, the following independent variables were derived from age 7 to age 19: immigrant background, caries prevalence (DMFT values) at age 10, occurrence of dental anxiety, and missed or cancelled appointments before endodontic treatment. The outcome variable was presence or absence of endodontic treatment due to caries. Bivariate analysis and a multiple logistic regression model were used to analyse the data. RESULTS: In the bivariate analyses, all independent variables except cancelled appointments were statistically significantly associated with future endodontic treatment. Of these, immigrant background did not remain as a statistically significant factor in the multiple regression model. The highest odds ratios were 4.3 for >2 DMFT at age 10 and 4.1 for >20% missed appointments. CONCLUSION: In the present sample, with a relatively high proportion of individuals with an immigrant background, >2 DMFT at age 10, many missed appointments and dental anxiety were all risk indicators for future endodontic treatment due to caries up to age 19.

Periapical status and technical quality of root-filled teeth in Swedish adolescents and young adults. A retrospective study.

OBJECTIVE: The aim was to study periapical status and the technical quality of root-filled teeth in Swedish adolescents and young adults in Malmö, Sweden. MATERIAL AND METHODS: The sample, collected from dental records in the Public Dental Service, consisted of notes and radiographs of all root-filled permanent teeth in all 19-year-olds born in 1979 (mean age at root filling=16.2 years). The sample for assessing periapical status and technical quality consisted of 124-153 teeth. The criterion for inclusion for assessing periapical status was a follow-up time of at least one year. Periapical status was assessed with the Periapical Index (PAI). Technical quality was analyzed from radiographs in two respects: sealing quality of the root canal and distance from the root filling to the radiographic apex. The radiographs were analyzed independently by two observers with inter-examiner kappa values of 0.82-0.85. RESULTS: Apical periodontitis was found in 52% of the teeth and occurred significantly more often among molars than among anterior teeth. As judged radiographically, 51% of the teeth were inadequately sealed. In 38%, the distance to the apex was >2 mm and overfilling was registered in 14% of the teeth. Compared with anterior teeth, significantly more root fillings of molars had a distance to the apex of >2 mm. Technical quality was statistically significantly correlated with periapical status at follow-up. CONCLUSIONS: The technical quality and periapical status of root-filled teeth in adolescents and young adults were unsatisfactory in about half of the teeth.

Bitewing examination to detect caries in children and adolescents--when and how often?

UNLABELLED: It is generally agreed that the decision to take bitewing radiographs for detecting caries should be based on the benefit to the individual patient in relation to the risks associated with low dose radiation exposure and the costs. There is incomplete knowledge about the effectiveness of various methods for selecting individuals who will benefit from bitewing examination. Available knowledge suggests, however, that our ability to identify correctly those who will benefit is limited. It may, therefore, be more effective to combine population- and individual-based selection criteria. For this purpose, four key ages and individual-based criteria between the key ages are suggested. CLINICAL RELEVANCE: The purpose of the presented selection criteria are to improve the dental practioner's effectiveness in selecting patients who will benefit from bitewing examination, thereby reducing the number of arbitrary and 'just in case' radiographs and the radiation dose.

Caries-preventive effect of sodium fluoride mouthrinses: a systematic review of controlled clinical trials.

The Swedish Council on Technology Assessment in Health Care launched a project group in 1999 to systematically review and evaluate the existing literature on different caries-preventive methods. The aim of this article was to report the findings concerning the caries-preventive effect of fluoride mouthrinses (FMRs) in various age groups, with special reference to background fluorides. A systematic search in electronic databases for literature published between 1966 and August 2003 was conducted with the inclusion criteria of a randomized or controlled clinical trial, at least 2 years' follow-up, and caries increment in the permanent dentition (DeltaDMFS/T) as endpoint. Out of 174 articles originally identified, 62 met the inclusion criteria. These studies were assessed independently by at least two reviewers and scored A-C according to predetermined criteria for methodology and performance. The measure of effect was the prevented fraction (PF) expressed as percent. The level of evidence was based on 25 articles. The results revealed limited evidence (evidence level 3) for the caries-preventive effect (PF 29%) of daily or weekly sodium fluoride rinses compared with placebo in permanent teeth of schoolchildren and adolescents with no additional fluoride exposure and for a caries-preventive effect on root caries in older adults. Inconclusive evidence (evidence level 4) was found regarding the effect of FMRs in schoolchildren and adolescents exposed to additional fluoride sources such as daily use of fluoride toothpaste. No firm support for the use of FMRs was disclosed in a small number of studies designed for patients at caries risk. Furthermore, no association between the frequency of the rinses and prevented fraction or saved surfaces per year was found. In conclusion, this systematic review suggests that sodium fluoride mouthrinses may have an anti-caries effect in children with limited background of fluoride exposure, while its additional effect in children with daily use of fluoride toothpaste could be questioned. The need for further clinical trials to elucidate the effect of FMRs in risk patients and older adults is emphasized.

Effect of combined caries-preventive methods: a systematic review of controlled clinical trials.

The aim of this systematic review was to evaluate the caries-preventive effect of combined caries-preventive methods, defined as two or more different interventions in combination, each expected to prevent dental caries. The Medline database was searched for articles published in the period January 1966 to June 2003. Twenty-four controlled studies met the inclusion criteria, and their value as evidence was assessed according to predetermined criteria. The level of evidence for the overall conclusion regarding each method was graded according to the protocol of the Swedish Council on Technology Assessment in Health Care. The scientific evidence for the combination of treatments involving fluoride that had a preventive effect on caries in children and adolescents was graded as moderate. However, for elderly patients the scientific evidence for the caries-preventive effect of different combinations of treatments was found to be incomplete. No conclusion could be drawn regarding the evidence for combinations of treatments being effective for groups at high caries risk, as the results from the identified clinical studies were conflicting.

Professional fluoride varnish treatment for caries control: a systematic review of clinical trials.

The aim of this paper was systematically to evaluate the caries-preventive effect of professional fluoride varnish treatments. A search of the literature for articles published between 1966 and August 2003 was carried out in electronic databases, reference lists of articles, and selected textbooks in accordance with the strategy of the Swedish Council on Technology Assessment in Health Care. Out of 302 identified papers, 24 randomized and controlled clinical trials comparing fluoride varnish with placebo, no active treatment or other fluoride preventive regimens of at least 2 years' study duration were included. The trials that met the inclusion criteria were assessed independently and systematically by at least two reviewers and scored from A to C according to predetermined criteria for methodology and performance. The main outcome measure was the preventive fraction expressed as a percentage. The results displayed limited evidence (evidence level 3) for the caries preventive effect of topical applications of fluoride varnishes in permanent teeth. The average prevented fraction was 30% (0-69%) when compared with untreated controls. Inconclusive evidence (evidence level 4) was found for fluoride varnish treatment in the primary dentition and in adults. This systematic review reinforces the need for future dinical research of high quality, incorporating modern concepts of dinical performance and evaluation to assess dental caries control using professional fluoride varnish.

Caries incidence rates in Swedish adolescents and young adults with particular reference to adjacent approximal tooth surfaces: a methodological study.

OBJECTIVES: The objective was to assess the dependence of the caries status of the adjacent approximal surface on the incidence of approximal caries. METHODS: At baseline, the material consisted of a cohort of 536 Swedish children. The individuals were followed through annual bitewing radiographs from the age of 11-13 to 21-22 years. A radiographic scoring system was used to assess the caries status of the surfaces: scores 0 and 1 = sound surface to score 4 = caries in the outer half of the dentine. A model was used to calculate the dependence of the caries status of adjacent approximal tooth surfaces. The unit of analysis was a pair of adjacent approximal surfaces and in all, 12 pairs of posterior approximal surfaces were analysed. RESULTS: The individual caries rates of the 24 posterior approximal surfaces ranged from 1.3 to 8.3 new caries lesions per 100 tooth surface-years. The caries rate of an approximal tooth surface depended on the caries status of the adjacent surface: a sound surface next to a sound surface had a relatively small risk of developing caries, while the risk increased 1.6-32.3 times if the adjacent surface was in a caries state as judged radiographically. The distal surface of the first molar developed caries more often than the mesial surface of the second molar. CONCLUSIONS: The caries rate of an approximal tooth surface was 1.6-32.3 times higher if the adjacent surface was in a caries state compared to when the latter was sound.

Caries-preventive effect of fissure sealants: a systematic review.

The objectives of this study were to evaluate systematically the evidence of the caries-preventive effect of fissure sealing of occlusal tooth surfaces and to examine factors potentially modifying the effect. The search strategies included electronic databases, reference lists of articles, and selected textbooks. Inclusion criteria were randomized or quasi-randomized clinical trials or controlled clinical trials comparing fissure sealing with no treatment or another preventive treatment in children up to 14 years of age at the start; the outcome measure was caries increment; the diagnostic criteria had been described; and the follow-up time was at least 2 years. Inclusion decisions were taken and grading of the studies was done independently by two of the authors. The main measure of effect was relative risk reduction. Thirteen studies using resin-based or glass ionomer sealant materials were included in the final analysis. The results showed that most studies were performed during the 1970s and a single application had been utilized. The relative caries risk reduction pooled estimate of resin-based sealants on permanent 1st molars was 33% (relative risk = 0.67; CI = 0.55-0.83). The effect depended on retention of the sealant. In conclusion, the review suggests limited evidence that fissure sealing of 1st permanent molars with resin-based materials has a caries-preventive effect. The evidence is incomplete for permanent 2nd molars, premolars and primary molars and for glass ionomer cements. Overall, there remains a need for further trials of high quality, particularly in child populations with a low and a high caries risk, respectively.

Dietary factors in the prevention of dental caries: a systematic review.

The aim of this study was, systematically, to evaluate the effect of dietary changes in the prevention of dental caries. A search and analysis strategy was followed, as suggested by the Swedish Council on Technology Assessment in Health Care (SBU). The search strategy for articles published in 1966-2003 was performed using electronic databases and reference lists of articles and selected textbooks. Out of 714 articles originally identified, 18 met the inclusion criteria for a randomized or controlled clinical trial--at least 2 years' follow-up and caries increment as a primary endpoint. This included the total or partial substitution of sucrose with sugar substitutes or the addition of protective foods to chewing gum. No study was found evaluating the effect of information designed to reduce sugar intake/frequency as a single preventive measure. It is suggested that the evidence for the use of sorbitol or xylitol in chewing gum, or for the use of invert sugar, is inconclusive. No caries-preventive effect was found from adding calcium phosphate or dicalcium phosphate dihydrate to chewing gums. The review dearly demonstrates the need for well-designed randomized clinical studies with adequate control groups and high compliance.